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Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a crucial enzyme in the glycolysis pathway, possessing both kinase and phosphatase capabilities. Although it has emerged as an important oncogene in various cancer types, its function in oral squamous cell carcinoma (OSCC) is still not well understood. In our research, PFKFB4 expression was assessed via immunohistochemical (IHC) staining of tissue microarrays and OSCC patient specimens. The transcriptional expression of PFKFB4 in OSCC was analyzed by utilizing The Cancer Genome Atlas (TCGA) dataset. Correlation between PFKFB4 expression and clinicopathological features was examined using the χ2 test. Prognostic investigation of PFKFB4 was conducted via Kaplan-Meier and Cox analyses. PFKFB4 levels were notably elevated in OSCC samples in comparison to adjacent normal tissues (P < 0.001). Elevated PFKFB4 expression was associated with higher histologic grade (P = 0.0438), higher T stage (P = 0.031), and more advanced clinical stage (P = 0.0063). The ROC curve demonstrated the diagnostic potential of PFKFB4 (AUC = 0.827). Increased levels of PFKFB4 were linked to decreased overall survival (OS) (P = 0.04), poorer disease-specific survival (DSS) (P = 0.04), and shorter progression-free interval (PFI) (P < 0.001). PFKFB4 expression was identified as an independent risk factor for OS based on Cox regression analysis [hazard ratio (HR) = 1.517, P = 0.044)]. An OS nomogram was constructed with a concordance index of 0.690. Our findings reveal that upregulated PFKFB4 expression in OSCC tissues could serve as a potential prognostic biomarker.
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Biomarcadores de Tumor , Carcinoma de Células Escamosas , Estimación de Kaplan-Meier , Neoplasias de la Boca , Fosfofructoquinasa-2 , Humanos , Fosfofructoquinasa-2/genética , Fosfofructoquinasa-2/metabolismo , Femenino , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/diagnóstico , Masculino , Pronóstico , Persona de Mediana Edad , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Curva ROC , Modelos de Riesgos Proporcionales , Regulación Neoplásica de la Expresión Génica , Anciano , InmunohistoquímicaRESUMEN
Trichosporon species are part of the normal microbiota of humans which can cause both superficial and invasive infections, primarily affecting immunocompetent and immunocompromised hosts, respectively. Giant ulcer caused by Trichosporon asahii is relatively uncommon in immunocompetent hosts. Increased drug resistance and biofilm-associated virulence makes the treatment of infectious ulcers challenging. Herein, we present a case of a massive ulcer caused by T. asahii which resulted in completed healing when treated with photodynamic therapy (PDT) and voriconazole. It provided the feasibility for PDT combined with antifungal drugs to treat similar refractory cases.
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Pentachlorophenol (PCP) was once used as a pesticide, germicide, and preservative due to its stable properties and resistance to degradation. This study aimed to design a biosensor for the quantitative and prompt detection of capable of PCP. A cell-free fluorescence biosensor was developed while employing NalC, an allosteric Transcription Factor responsive to PCP and In Vitro Transcription. By adding a DNA template and PCP and employing Electrophoretic Mobility Shift Assay while monitoring the dynamic fluorescence changes in RNA, this study offers evidence of NalC's potential applicability in sensor systems developed for the specific detection of PCP. The biosensor showed the capability for the quantitative detection of PCP, with a Limit of Detection (LOD) of 0.21 µM. Following the addition of Nucleic Acid Sequence-Based Amplification, the fluorescence intensity of RNA revealed an excellent linear relationship with the concentration of PCP, showing a correlation coefficient (R2) of 0.9595. The final LOD was determined to be 0.002 µM. This study has successfully translated the determination of PCP into a fluorescent RNA output, thereby presenting a novel approach for detecting PCP within environmental settings.
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RATIONALE: In the era of burgeoning digital technology, healthcare is a challenging transformative change towards virtual and digital platforms. Internet-based healthcare services are emerging as a popular trend within the medical area. User experience (UX) is paramount for the healthcare service, as it significantly influences experience satisfaction and fosters user viscosity. Gaining a profound understanding of users' demands and crafting services that align with their expectations is essential. METHODS: Consequently, exploring an effective design approach for the digital healthcare service that prioritizes UX along with utilizing a comprehensive evaluation methodology to handle UX data, is of profound importance. This study introduces a design methodology for Internet-based healthcare products grounded in the UX and mental (UX-M) model. Aiming to refine the Internet-based healthcare product design by integrating insights from the experience data, it employs the Delphi-ANP and the fuzzy comprehensive evaluation to determine evaluation indexes and conduct experiential assessments. RESULTS: The UX evaluation results of existing schemes are compared with the proposed design scheme of the intelligent guidance and internet hospital. The findings indicate that the UX evaluation of Internet-based medical services with the proposed method outperforms the existing schemes. CONCLUSIONS: On the one hand, UX research of Internet-based healthcare products can significantly enhance service satisfaction for patients utilizing online medical treatments. On the other hand, the analysis of experience-based evaluation empowers designers to refine and improve UX design of Internet-based medical services. Such research endeavors are critical for enhancing the overall quality of service offerings and elevating user satisfaction in the digital healthcare landscape.
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Allylic amines are prevalent and vital structural components present in many bioactive compounds and natural products. Additionally, they serve as valuable intermediates and building blocks, with wide-ranging applications in organic synthesis. However, direct α-C(sp3)-H alkenylation of feedstock amines, particularly for the preparation of α-alkenylated cyclic amines, has posed a longstanding challenge. Herein, we present a general, mild, operationally simple, and transition-metal-free α-alkenylation of various readily available amines with alkenylborate esters in excellent E/Z - and diastereoselectivities. This method features good compatibility with water and oxygen, broad substrate scope, and excellent functional group tolerance, thereby enabling the late-stage modification of various complex molecules. Mechanistic studies suggest that the formation of a photoactive electron donor-acceptor complex between 2-iodobenzamide and the tetraalkoxyborate anion, which subsequently undergoes photoinduced single electron transfer and intramolecular 1,5-hydrogen atom transfer to generate the crucial α-amino radicals, is the key to success of this chemistry.
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Miao sour soup (MSS), a daily fermented food in Guizhou, China, is rich in microorganisms with various beneficial activities, including anti-inflammatory and antioxidant activities. However, the therapeutic effects of MSS on IBD remain unexplored. This study aimed to investigate the protective effect of MSS against colitis in mice. In this study, we examined the microbial community structure of MSS by metagenomic sequencing and also explored the protective effect of MSS on DSS-induced colitis in mice. We investigated the effects of MSS on intestinal inflammatory response and intestinal barrier function in mice. Finally, the changes in intestinal flora were analyzed based on the 16S rRNA gene sequencing results. Significantly, the experiment result shows that MSS ameliorated the severity of DSS-induced disease in mice by mitigating colitis-associated weight loss, reducing the disease activity index of IBD, alleviating colonic hemorrhagic lesions, increasing colon length, and improving colonic tissue damage. Moreover, MSS preserved intestinal barrier integrity and restored intestinal epithelial function in mice. Additionally, MSS modulated the structure and composition of the intestinal flora. Furthermore, MSS downregulated pro-inflammatory factors and attenuated the NF-κB p65 expression, thereby mitigating the inflammatory response. These findings highlight the protective effect of MSS against DSS-induced colitis, providing substantial scientific support for potential applications of MSS as a functional food.
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Colitis , Sulfato de Dextran , Microbioma Gastrointestinal , Mucosa Intestinal , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Colitis/inducido químicamente , Sulfato de Dextran/efectos adversos , Masculino , Mucosa Intestinal/microbiología , Ratones Endogámicos C57BL , Alimentos Fermentados , Modelos Animales de Enfermedad , Colon/microbiología , Colon/metabolismo , ARN Ribosómico 16S/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Funcion de la Barrera IntestinalRESUMEN
Virus-induced drought tolerance presents a fascinating facet of biotic-abiotic interaction in plants, yet its molecular intricacies remain unclear. Our study shows that cowpea mild mottle virus (CPMMV) infection enhances drought tolerance in common bean (Phaseolus vulgaris) plants through a virus-derived small interfering RNA (vsiRNA)-activated autophagy pathway. Specifically, a 21-bp vsiRNA originating from the CPMMV Triple Gene Block1 (TGB1) gene targeted the 5' untranslated region (UTR) of the host Teosinte branched 1, Cycloidea, Proliferating Cell Factor (TCP) transcription factor gene PvTCP2, independent of the known role of TGB1 as an RNA silencing suppressor. This targeting attenuated the expression of PvTCP2, which encodes a transcriptional repressor, and in turn upregulated the core autophagy-related gene (ATG) PvATG8c, leading to activated autophagy activity surpassing the level induced by drought or CPMMV infection alone. The downstream EARLY RESPONSIVE TO DEHYDRATION (ERD) effector PvERD15 is a homologue of Arabidopsis thaliana AtERD15, which positively regulates stomatal aperture. PvERD15 was degraded in PvATG8c-mediated autophagy. Therefore, we establish a TGB1-PvTCP2-PvATG8c-PvERD15 module as a trans-kingdom fine-tuning mechanism that contributes to virus-induced drought tolerance in plant-drought-virus interactions.
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Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions. Different mutations on a single ASD gene contribute to heterogeneity of disease phenotypes, possibly due to functional diversity of generated isoforms. SHANK2, a causative gene in ASD, demonstrates this phenomenon, but there is a scarcity of tools for studying endogenous SHANK2 proteins in an isoform-specific manner. Here, we report a point mutation on SHANK2, which is found in a patient with autism, located on exon of the SHANK2B transcript variant (NM_133266.5), hereby SHANK2BY29X. This mutation results in an early stop codon and an aberrant splicing event that impacts SHANK2 transcript variants distinctly. Induced pluripotent stem cells (iPSCs) carrying this mutation, from the patient or isogenic editing, fail to differentiate into functional dopamine (DA) neurons, which can be rescued by genetic correction. Available SMART-Seq single-cell data from human midbrain reveals the abundance of SHANK2B transcript in the ALDH1A1 negative DA neurons. We then show that SHANK2BY29X mutation primarily affects SHANK2B expression and ALDH1A1 negative DA neurons in vitro during early neuronal developmental stage. Mice knocked in with the identical mutation exhibit autistic-like behavior, decreased occupancy of ALDH1A1 negative DA neurons and decreased dopamine release in ventral tegmental area (VTA). Our study provides novel insights on a SHANK2 mutation derived from autism patient and highlights SHANK2B significance in ALDH1A1 negative DA neuron.
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Lymphocyte activation involves a transition from quiescence and associated catabolic metabolism to a metabolic state with noted similarities to cancer cells such as heavy reliance on aerobic glycolysis for energy demands and increased nutrient requirements for biomass accumulation and cell division 1-3 . Following antigen receptor ligation, lymphocytes require spatiotemporally distinct "second signals". These include costimulatory receptor or cytokine signaling, which engage discrete programs that often involve remodeling of organelles and increased nutrient uptake or synthesis to meet changing biochemical demands 4-6 . One such signaling molecule, IL-4, is a highly pleiotropic cytokine that was first identified as a B cell co-mitogen over 30 years ago 7 . However, how IL-4 signaling mechanistically supports B cell proliferation is incompletely understood. Here, using single cell RNA sequencing we find that the cholesterol biosynthetic program is transcriptionally upregulated following IL-4 signaling during the early B cell response to influenza virus infection, and is required for B cell activation in vivo . By limiting lipid availability in vitro , we determine cholesterol to be essential for B cells to expand their endoplasmic reticulum, progress through cell cycle, and proliferate. In sum, we demonstrate that the well-known ability of IL-4 to act as a B cell growth factor is through a previously unknown rewiring of specific lipid anabolic programs, relieving sensitivity of cells to environmental nutrient availability.
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The ATP-dependent caseinolytic protease (Clp) system has been reported to play an important role in plant growth, development, and defense against pathogens. However, whether the Clp system is involved in plant defense against herbivores remains largely unclear. We explore the role of the Clp system in rice defenses against brown planthopper (BPH) Nilaparvata lugens by combining chemical analysis, transcriptome, and molecular analyses, as well as insect bioassays. We found the expression of a rice Clp proteolytic subunit gene, OsClpP6, was suppressed by infestation of BPH gravid females and mechanical wounding. Silencing OsClpP6 enhanced the level of BPH-induced jasmonic acid (JA), JA-isoleucine (JA-Ile), and ABA, which in turn promoted the production of BPH-elicited rice volatiles and increased the resistance of rice to BPH. Field trials showed that silencing OsClpP6 decreased the population densities of BPH and WBPH. We also observed that silencing OsClpP6 decreased chlorophyll content in rice leaves at early developmental stages and impaired rice root growth and seed setting rate. These findings demonstrate that an OsClpP6-mediated Clp system in rice was involved in plant growth-defense trade-offs by affecting the biosynthesis of defense-related signaling molecules in chloroplasts. Moreover, rice plants, after recognizing BPH infestation, can enhance rice resistance to BPH by decreasing the Clp system activity. The work might provide a new way to breed rice varieties that are resistant to herbivores.
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Ciclopentanos , Hemípteros , Oryza , Oxilipinas , Femenino , Animales , Proteasas ATP-Dependientes , Oryza/genética , Fitomejoramiento , Péptido Hidrolasas , Isoleucina , Hemípteros/genética , Adenosina TrifosfatoRESUMEN
AIMS AND OBJECTIVES: To assess the prognostic accuracy of the surprise question (SQ) when used by nurses working in hospital wards to determine 1-year mortality in acutely hospitalised older patients. BACKGROUND: The predictive accuracy of the SQ, when used by general nurses caring for older hospitalised patients, has not been comprehensively studied. DESIGN: A prospective cohort study. METHODS: This cohort study recruited consecutive 10,139 older patients (aged ≥65 years) who were admitted to Taipei City Hospital and were evaluated for the needs of palliative care in 2015. All patients were followed up for 12 months or until their death. The c-statistic value was calculated to indicate the predictive accuracy of the SQ and Palliative Care Screening Tool (PCST). RESULTS: Of all participants, 18.8% and 18.6% had a SQ response of 'no' and a PCST score ≥4, respectively. After controlling for other covariates, an SQ response of 'no' (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.83-2.31) and a PCST score ≥4 (AHR = 1.50; 95% CI: 1.29-1.75) were found to be the independent predictors for patients' 12-month mortality. The C-statistic values of the SQ and the PCST at recognising patients in their last year of life were .663 and .670, respectively. Moreover, there was moderate concordance (k = .44) between the SQ and the PCST in predicting 12-month mortality. CONCLUSIONS: SQ response of 'no' and a PCST score ≥4 were independent predictors of 12-month mortality in older patients. RELEVANCE TO CLINICAL PRACTICE: The SQ, when used by nurses working in hospital wards, is effective in identifying older patients nearing the end of life, as well as in providing advance care planning for patients. PATIENT OR PUBLIC CONTRIBUTION: Patients' palliative care needs at admission were assessed by general nurses using the SQ and PCST.
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Resistant crop cultivars can recruit beneficial rhizobacteria to resist disease. However, whether this recruitment is regulated by quantitative trait loci (QTL) is unclear. The role of QTL in recruiting specific bacteria against bacterial wilt (BW) is an important question of practical significance to disease management. Here, to identify QTL controlling BW resistance, Super-BSA was performed in F2 plants derived from resistant eggplant cultivar R06112 × susceptible cultivar S55193. The QTL was narrowed down through BC1F1-BC3F1 individuals by wilting symptoms and KASP markers. Rhizosphere bacterial composition of R06112, S55193, and resistant individuals EB158 (with the QTL) and susceptible individuals EB327 (without QTL) from BC2F1 generation were assessed by Illumina sequencing-based analysis, and the activation of plant immunity by the bacterial isolates was analyzed. Evidence showed that BW-resistant is controlled by one QTL located at the 270 kb region on chromosome 10, namely EBWR10, and nsLTPs as candidate genes confirmed by RNA-Seq. EBWR10 has a significant effect on rhizobacteria composition and significantly recruits Bacillus. pp. A SynCom of three isolated Bacillus. pp trains significantly reduced the disease incidence, changed activities of CAT, PPO, and PAL and concentration of NO, H2O2, and O2-, activated SA and JA signaling-dependent ISR, and displayed immune activation against Ralstonia solanacearum in eggplant. Our findings demonstrate for the first time that the QTL can recruit beneficial rhizobacteria, which jointly promote the suppression of BW. This method charts a path to develop the QTL in resistant cultivar-driven probiotics to ameliorate plant diseases.
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The fibroblast growth factor receptor (FGFR) signaling pathway plays important roles in cellular processes such as proliferation, differentiation, and migration. In this study, we highlighted the potential of FGFR inhibitors bearing the (S)-3,3-difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene scaffold containing a crucial 3-pyridyl group for the treatment of FGFR mutant cancers. The representative compound (S)-23, which was identified through comprehensive evaluation, exhibited potent antiproliferative activity with GI50 in the range of 6.4-10.4 nM against FGFR1 fusion protein-carrying, FGFR2-amplified, and FGFR2 mutant cancer cell lines and good antiproliferative activity against FGFR3 translocation and mutant FGFR4 cancer cell lines, as well as potency assessment against FGFR1-4 kinases. Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.
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Antineoplásicos , Neoplasias , Humanos , Ratones , Animales , Antineoplásicos/farmacología , Receptores de Factores de Crecimiento de Fibroblastos , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Neoplasias/tratamiento farmacológico , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Transducción de Señal , Línea Celular , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Dedicator of cytokinesis 8 (DOCK8) mutations lead to a primary immunodeficiency associated with recurrent gastrointestinal infections and poor antibody responses but, paradoxically, heightened IgE to food antigens, suggesting that DOCK8 is central to immune homeostasis in the gut. Using Dock8-deficient mice, we found that DOCK8 was necessary for mucosal IgA production to multiple T cell-dependent antigens, including peanut and cholera toxin. Yet DOCK8 was not necessary in T cells for this phenotype. Instead, B cell-intrinsic DOCK8 was required for maintenance of antigen-specific IgA-secreting plasma cells (PCs) in the gut lamina propria. Unexpectedly, DOCK8 was not required for early B cell activation, migration, or IgA class switching. An unbiased interactome screen revealed novel protein partners involved in metabolism and apoptosis. Dock8-deficient IgA+ B cells had impaired cellular respiration and failed to engage glycolysis appropriately. These results demonstrate that maintenance of the IgA+ PC compartment requires DOCK8 and suggest that gut IgA+ PCs have unique metabolic requirements for long-term survival in the lamina propria.
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Factores de Intercambio de Guanina Nucleótido , Inmunoglobulina A , Mucosa Intestinal , Ratones Noqueados , Células Plasmáticas , Animales , Ratones , Factores de Intercambio de Guanina Nucleótido/metabolismo , Factores de Intercambio de Guanina Nucleótido/genética , Inmunoglobulina A/metabolismo , Inmunoglobulina A/inmunología , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Activación de Linfocitos , Linfocitos B/inmunología , Linfocitos B/metabolismo , Glucólisis , Ratones Endogámicos C57BL , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
The demand for large electromechanical performance in lead-free polycrystalline piezoelectric thin films is driven by the need for compact, high-performance microelectromechanical systems (MEMS) based devices operating at low voltages. Here we significantly enhance the electromechanical response in a polycrystalline lead-free oxide thin film by utilizing lattice-defect-induced structural inhomogeneities. Unlike prior observations in mismatched epitaxial films with limited low-frequency enhancements, we achieve large electromechanical strain in a polycrystalline (K,Na)NbO3 film integrated on silicon. This is achieved by inducing self-assembled Nb-rich planar faults with a nonstoichiometric composition. The film exhibits an effective piezoelectric coefficient of 565 pm V-1 at 1 kHz, surpassing those of lead-based counterparts. Notably, lattice defect growth is substrate-independent, and the large electromechanical response is extended to even higher frequencies in a polycrystalline film. Improved properties arise from unique lattice defect morphology and frequency-dependent relaxation behavior, offering a new route to remarkable electromechanical response in polycrystalline thin films.
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Lycopene is widely used in cosmetics, food, and nutritional supplements. Microbial production of lycopene has been intensively studied. However, few metabolic engineering studies on Pichia pastoris have been aimed at achieving high-yield lycopene production. In this study, the CRISPR/Cpf1-based gene repression system was developed and the gene editing system was optimized, which were applied to improve lycopene production successfully. In addition, the sterol regulatory element-binding protein SREBP (Sre) was used for the regulation of lipid metabolic pathways to promote lycopene overproduction in P. pastoris for the first time. The final engineered strain produced lycopene at 7.24 g/L and 75.48 mg/g DCW in fed-batch fermentation, representing the highest lycopene yield in P. pastoris reported to date. These findings provide effective strategies for extended metabolic engineering assisted by the CRISPR/Cpf1 system and new insights into metabolic engineering through transcriptional regulation of related metabolic pathways to enhance carotenoid production in P. pastoris.
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Ingeniería Metabólica , Saccharomycetales , Licopeno/metabolismo , Pichia/genética , Pichia/metabolismo , Saccharomycetales/metabolismoRESUMEN
Picornavirus hepatitis A virus (HAV) is a common cause of hepatitis worldwide. It is spread primarily through contaminated food and water or person-to-person contact. HAV I has been identified as the most common type of human HAV infection. Here, we have developed a cell-free toehold switch sensor for HAV I detection. We screened 10 suitable toehold switch sequences using NUPACK software, and the VP1 gene was used as the target gene. The optimal toehold switch sequence was selected by in vivo expression. The best toehold switch concentration was further found to be 20 nM in a cell-free system. 5 nM trigger RNA activated the toehold switch to generate visible green fluorescence. The minimum detection concentration decreased to 1 pM once combined with NASBA. HAV I trigger RNA could be detected accurately with excellent specificity. In addition, the cell-free toehold switch sensor was verified in HAV I entities. The successful construction of the cell-free toehold switch sensor provided a convenient, rapid, and accurate method for HAV I on-site detection, especially in developing countries, without the involvement of expensive facilities and additional professional operators.
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Virus de la Hepatitis A , Hepatitis A , Humanos , Virus de la Hepatitis A/genética , Hepatitis A/diagnóstico , Virus de la Hepatitis A Humana/genética , ARNRESUMEN
Cowpea mild mottle virus (CPMMV) is a global plant virus that poses a threat to the production and quality of legume crops. Early and accurate diagnosis is essential for effective managing CPMMV outbreaks. With the advancement in isothermal recombinase polymerase amplification and lateral flow strips technologies, more rapid and sensitive methods have become available for detecting this pathogen. In this study, we have developed a reverse transcription recombinase polymerase amplification combined with lateral flow strips (RT-RPA-LFS) method for the detection of CPMMV, specifically targeting the CPMMV coat protein (CP) gene. The RT-RPA-LFS assay only requires 20 min at 40°C and demonstrates high specificity. Its detection limit was 10 copies/µl, which is approximately up to 100 times more sensitive than RT-PCR on agarose gel electrophoresis. The developed RT-RPA-LFS method offers a rapid, convenient, and sensitive approach for field detection of CPMMV, which contribute to controlling the spread of the virus.
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Children's dental fear (CDF) has become one of the main reasons affecting the quality of dental treatment. In order to reduce the incidence of CDF in China before and after children's dental visits, this review applies literature analysis and empirical summary methods to analyze and summarize academic discussions on this topic, including occurrence mechanism, prevention guidance, and the conclusion that the occurrence and prevention of CDF is closely related with children's internal characteristics and external influences. In the end, we propose a breakthrough of combining the CFSS-DS scale and three-grade prevention theory together in the future to provide new ideas and hypotheses for the prevention of CDF.
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Mitochondria are dynamic organelles that are important for cell growth and proliferation. Dysregulated mitochondrial dynamics are highly associated with the initiation and progression of various cancers, including ovarian cancer. However, the regulatory mechanism underlying mitochondrial dynamics is still not fully understood. Previously, our study showed that carnitine palmitoyltransferase 1A (CPT1A) is highly expressed in ovarian cancer cells and promotes the development of ovarian cancer. Here, we find that CPT1A regulates mitochondrial dynamics and promotes mitochondrial fission in ovarian cancer cells. Our study futher shows that CPT1A regulates mitochondrial fission and function through mitochondrial fission factor (MFF) to promote the growth and proliferation of ovarian cancer cells. Mechanistically, we show that CPT1A promotes succinylation of MFF at lysine 302 (K302), which protects against Parkin-mediated ubiquitin-proteasomal degradation of MFF. Finally, the study shows that MFF is highly expressed in ovarian cancer cells and that high MFF expression is associated with poor prognosis in patients with ovarian cancer. MFF inhibition significantly inhibits the progression of ovarian cancer in vivo. Overall, CPT1A regulates mitochondrial dynamics through MFF succinylation to promote the development of ovarian cancer. Moreover, our findings suggest that MFF is a potential therapeutic target for ovarian cancer.